OBJECTIVE To investigate the role of clinical pharmacists in the individualized treatment of a rare case of diffuse pulmonary microabscesses caused by Streptococcus constellatus complicated with organizing pneumonia （OP） in a non-immunocompromised patient. METHODS For a middle-aged， non-immunocompromised patient with a one-year disease course， whose imaging findings showed the coexistence of diffuse microabscesses and OP caused by S. constellatus pulmonary abscess， the clinical pharmacist， based on pharmacokinetics/pharmacodynamics characteristics， assisted the physician in optimizing the previously ineffective anti-infective regimen to Ceftriaxone sodium for injection combined with Metronidazole and sodium chloride injection， so as to enhance coverage of mixed anaerobes and lesion penetration. After the patient’s hemoptysis ceased， the clinical pharmacist recommended timely initiation of low-dose Methylprednisolone sodium succinate for injection to manage OP. Upon discharge， sequential oral therapy with Linezolid tablets， Metronidazole tablets， Methylprednisolone tablets and Omeprazole enteric-coated tablets was prescribed. RESULTS After implementation of the individualized treatment regimen， the patient’s hemoptysis resolved， pulmonary lesions significantly regressed， and the patient was discharged in a stable condition. At the three-month follow-up， the patient remained stable. CONCLUSIONS For chronic persistent pulmonary infection complicated with OP in a non-immunocompromised host， clinical pharmacists assist clinicians in optimizing anti-infective regimens and recommend the timely initiation of anti-inflammatory therapy after infection control， thereby contributing to favorable clinical outcomes. Individualized treatment of such complex cases requires comprehensive consideration of pathogen coverage， pathological barriers， and the timing of anti-inflammatory intervention.

Objective To identify key proteins associated with sudden cardiac death(SCD)caused by lethal arrhythmia and to explore their potential molecular mechanisms through integrated proteomic analysis,data mining,and bioinformatics.Methods A lethal arrhythmia model was established in 8-week-old male Sprague-Dawley rats,which were divided into an arrhythmia group and a control group.Proteomic techniques were applied to identify and quantify proteins in left ventricular myocardial tissue,and differentially expressed proteins related to arrhythmia were screened.Key proteins were further identified through comparison with target proteins in databases combined with joint analyses.Bioinformatics methods were then used to investigate potential molecular mechanisms.Results A total of 356 differentially expressed proteins were identified,including 189 upregulated and 167 downregulated.Association analysis with target gene proteins identified 71 key proteins,and a protein-protein interaction network was constructed.GO enrichment and KEGG pathway analyses indicated that these key proteins were primarily involved in ion channel dysfunction,enhanced oxidative stress,and autonomic nervous system imbalance.Conclusion This study,through the integration of proteomics,data mining,and bioinformatics,revealed critical molecular mechanisms underlying SCD associated with lethal arrhythmia.These findings provide new perspectives and potential biomarkers for forensic identification and research on the mechanisms of death.

Objective To identify key proteins associated with sudden cardiac death(SCD)caused by lethal arrhythmia and to explore their potential molecular mechanisms through integrated proteomic analysis,data mining,and bioinformatics.Methods A lethal arrhythmia model was established in 8-week-old male Sprague-Dawley rats,which were divided into an arrhythmia group and a control group.Proteomic techniques were applied to identify and quantify proteins in left ventricular myocardial tissue,and differentially expressed proteins related to arrhythmia were screened.Key proteins were further identified through comparison with target proteins in databases combined with joint analyses.Bioinformatics methods were then used to investigate potential molecular mechanisms.Results A total of 356 differentially expressed proteins were identified,including 189 upregulated and 167 downregulated.Association analysis with target gene proteins identified 71 key proteins,and a protein-protein interaction network was constructed.GO enrichment and KEGG pathway analyses indicated that these key proteins were primarily involved in ion channel dysfunction,enhanced oxidative stress,and autonomic nervous system imbalance.Conclusion This study,through the integration of proteomics,data mining,and bioinformatics,revealed critical molecular mechanisms underlying SCD associated with lethal arrhythmia.These findings provide new perspectives and potential biomarkers for forensic identification and research on the mechanisms of death.

The fat mass and obesity-associated protein (FTO) is an RNA demethylase required for catalytic demethylation of N ⁶-methyladenosine (m⁶A); it is highly expressed and functions as an oncogene in acute myeloid leukemia (AML). Currently, the overarching objective of targeting FTO is to precisely inhibit the catalytic activity. Meanwhile, whether FTO degradation also exerts antileukemic effects remains unknown. Herein, we designed the first FTO-targeting proteolysis targeting chimera (PROTAC) degrader QP73 using our FTO inhibitor Dac85-which potently inhibits FTO demethylation in AML cell lines-as a warhead. Notably, QP73 significantly induced FTO degradation in a time-, dose-, and ubiquitin-proteasome system-dependent manner and had superior antiproliferative activities to the FTO inhibitor Dac85 in various AML cell lines. Moreover, QP73 treatment significantly increased m⁶A modification on mRNA, promoted myeloid differentiation, and induced apoptosis of AML cells. Quantitative proteomics analysis showed that QP73 induced complete FTO degradation, upregulating RARA and ASB2 abundance and downregulating CEBPA, MYC, PFKP, and LDHB levels in AML cells. Lastly, QP73 exhibited antileukemic activity by increasing m⁶A modification and decreasing FTO levels in xenograft AML tumors. This proof-of-concept study shows that FTO-targeting PROTAC degraders can regulate the FTO signaling pathway and have potential antileukemia applications.

Objective: To assess the efficacy and safety of polymyxin B in neutropenic patients with hematologic disorders who had refractory gram-negative bacterial bloodstream infection. Methods: From August 2021 to July 2022, we retrospectively analyzed neutropenic patients with refractory gram-negative bacterial bloodstream infection who were treated with polymyxin B in the Department of Hematology of the First Affiliated Hospital of the Soochow University between August 2021 to July 2022. The cumulative response rate was then computed. Results: The study included 27 neutropenic patients with refractory gram-negative bacterial bloodstream infections. Polymyxin B therapy was effective in 22 of 27 patients. The median time between the onset of fever and the delivery of polymyxin B was 3 days [interquartile range (IQR) : 2-5]. The median duration of polymyxin B treatment was 7 days (IQR: 5-11). Polymyxin B therapy had a median antipyretic time of 37 h (IQR: 32-70). The incidence of acute renal dysfunction was 14.8% (four out of 27 cases), all classified as "injury" according to RIFLE criteria. The incidence of hyperpigmentation was 59.3%. Conclusion: Polymyxin B is a viable treatment option for granulocytopenia patients with refractory gram-negative bacterial bloodstream infections.
Humans ; Polymyxin B/adverse effects* ; Retrospective Studies ; Gram-Negative Bacterial Infections/complications* ; Fever/drug therapy* ; Sepsis/drug therapy* ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/complications*

OBJECTIVE: This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China. METHODS: A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database. RESULTS: A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs. CONCLUSION The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.
Humans ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV-1/genetics* ; Cross-Sectional Studies ; Phylogeny ; Anti-HIV Agents/therapeutic use* ; Drug Resistance, Viral/genetics* ; HIV Infections/epidemiology* ; Mutation ; China/epidemiology* ; Prevalence ; Genotype

OBJECTIVE: This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline (BR) and the conventional treatment regimen (CR, not containing Bedaquiline) for the treatment of adults with multidrug-resistant tuberculosis (MDR-TB) in China. METHODS: A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years. The model parameter data were synthesized from the literature, the national TB surveillance information system, and consultation with experts. The incremental cost-effectiveness ratio (ICER) of BR vs. CR was determined. RESULTS: BR ( vs. CR) had a higher sputum culture conversion rate and cure rate and prevented many premature deaths (decreased by 12.8%), thereby obtaining more quality-adjusted life years (QALYs) (increased by 2.31 years). The per capita cost in BR was as high as 138,000 yuan, roughly double that of CR. The ICER for BR was 33,700 yuan/QALY, which was lower than China's 1× per capita Gross Domestic Product (GDP) in 2020 (72,400 yuan). CONCLUSION BR is shown to be cost effective. When the unit price of Bedaquiline reaches or falls below 57.21 yuan per unit, BR is expected to be the dominant strategy in China over CR.
Adult ; Humans ; Antitubercular Agents/therapeutic use* ; Cost-Effectiveness Analysis ; Cost-Benefit Analysis ; Tuberculosis, Multidrug-Resistant/drug therapy* ; China/epidemiology*

ObjectiveTo analyze the feasibility， reliability and validity of the disability assessment for dementia scale for the elderly. MethodsA total of 290 dementia patients from 17 survey sites in 13 districts and counties of Chengdu were enrolled by convenient sampling method， and they were assessed using demographic data inventory， Mini-Mental State Examination （MMSE）， Neuropsychiatric Inventory （NPI）， Physical Self-Maintenance Scale （PSMS） and disability assessment for dementia scale for the elderly. Cronbach's α coefficient， Spearman-Brown coefficient， Guttman split-half coefficient and test-retest reliability were used to evaluate the internal consistency of above scales. Criterion-related validity of the scale was analyzed based on MMSE， NPI and PSMS. ResultsA total of 276 patients （95.17%） completed valid questionnaires. The intraclass correlation coefficient of the total score and each dimension were between 0.828~0.976， the Spearman-Brown coefficient were between 0.790~0.917， the Guttman split-half coefficient were between 0.812~0.857， and the Cronbach’s α coefficient were between 0.737~0.886. The cognitive function dimension score was positively correlated with the MMSE score （r=0.948， P<0.01）， the mental behavior symptom dimension score was positively correlated with the NPI score （r=0.893， P<0.01）， and the daily living ability dimension score was positively correlated with the PSMS score （r=0.997， P<0.01）. The dimensions scores were positively correlated with the total score of the scale （r=0.634~0.841， P<0.05）. ConclusionDisability of dementia assessment scale has good feasibility， reliability and validity， which is a reliable tool to assess senile dementia and disability.

OBJECTIVE: The study aimed to analyze the applicability of the World Health Organization's exclusionary guidelines for Urinary creatinine (Ucr) in the general Chinese population, and to identify Ucr related factors. METHODS: We conduct a cross-sectional study using baseline data from 21,167 participants in the China National Human Biomonitoring Program. Mixed linear models and restricted cubic splines (RCS) were used to analyze the associations between explanatory variables and Ucr concentration. RESULTS: The geometric mean and median concentrations of Ucr in the general Chinese population were 0.90 g/L and 1.01 g/L, respectively. And 9.36% samples were outside 0.3-3.0 g/L, including 7.83% below the lower limit and 1.53% above the upper limit. Middle age, male, obesity, smoking, higher frequency of red meat consumption and chronic kidney disease were associated significantly with higher concentrations of Ucr. Results of the RCS showed Ucr was positively and linearly associated with body mass index, inversely and linearly associated with systolic blood pressure, diastolic blood pressure, triglycerides level, and glomerular filtration rate, and were non-linearly associated with triiodothyronine. CONCLUSION The age- and gender-specific cut-off values of Ucr that determine the validity of urine samples in the general Chinese population were recommended. To avoid introducing bias into epidemiologic associations, the potential predictors of Ucr observed in the current study should be considered when using Ucr to adjust for variations in urine dilution.
Middle Aged ; Male ; Humans ; Creatinine ; Cross-Sectional Studies ; Asian People ; Glomerular Filtration Rate ; China

Objective: To explore the efficacy and safety of real-world eribulin in the treatment of metastatic breast cancer. Methods: From December 2019 to December 2020, patients with advanced breast cancer were selected from Beijing Chaoyang District Sanhuan Cancer Hospital, Shandong Cancer Hospital, Peking University Cancer Hospital, Baotou Cancer Hospital, Shengjing Hospital Affiliated to China Medical University, and Cancer Hospital of Chinese Academy of Medical Sciences. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for multivariate analysis. Results: The median progression-free survival (PFS) of 77 patients was 5 months, the objective response rate (ORR) was 33.8%, and the disease control rate (DCR) was 71.4%. The ORR of patients with triple-negative breast cancer was 23.1%, and the DCR was 57.7%; the ORR of patients with Luminal breast cancer was 40.0%, and the DCR was 77.8%; the ORR of patients with HER-2 overexpression breast cancer was 33.3%, and the DCR was 83.3%. ORR of 50.0% and DCR of 66.7% for patients treated with eribulin as first to second line treatment, ORR of 29.4% and DCR of 76.5% for patients treated with third to fourth line and ORR of 28.6% and DCR of 71.4% for patients treated with five to eleven line. The ORR of patients in the eribulin monotherapy group was 40.0% and the DCR was 66.0%; the ORR of patients in the combination chemotherapy or targeted therapy group was 22.2% and the DCR was 81.5%. Patients with a history of treatment with paclitaxel, docetaxel, or albumin paclitaxel during the adjuvant phase or after recurrent metastasis had an ORR of 32.9% and a DCR of 69.9% when treated with eribulin. The treatment efficacy is an independent prognostic factor affecting patient survival (P<0.001). The main adverse reactions in the whole group of patients were Grade Ⅲ-Ⅳ neutrophil decline [29.9% (23/77)], and other adverse reactions were Grade Ⅲ-Ⅳ fatigue [5.2% (4/77)], Grade Ⅲ-Ⅳ peripheral nerve abnormality [2.6% (2/77)] and Grade Ⅲ-Ⅳ alopecia [2.6% (2/77)]. Conclusions: Eribulin still has good antitumor activity against various molecular subtypes of breast cancer and advanced breast cancer that has failed multiple lines of chemotherapy, and the adverse effects can be controlled, so it has a good clinical application value.
Breast Neoplasms/pathology* ; Female ; Furans/adverse effects* ; Humans ; Ketones/adverse effects* ; Paclitaxel/adverse effects* ; Treatment Outcome ; Triple Negative Breast Neoplasms/drug therapy*